High Dose Omega 3 in People at Risk for Dementia
Primary Purpose
Dementia, Inflammation, Mild Cognitive Impairment
Status
Unknown status
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Omega-3 capsules
Olive oil
Sponsored by
About this trial
This is an interventional prevention trial for Dementia
Eligibility Criteria
Inclusion Criteria:
- Age > 50 years
- SCD or MCI
- No evidence of neurodegeneration (i.e. CSF phospho and total tau-levels below cut-off)
- Scandinavian mother tongue
- Completed 2-year follow-up in the DDI-study
- Stable medication for at least 3 months prior to baseline exam
Exclusion Criteria:
- Dementia (defined as MMSE < 26 and/or CDR >/= 1))
- Other dementia giving disease than AD
- Other brain disease
- Significant depression
- Unstable coronary heart disease or heart failure in need of treatment
- Systemic inflammatory diseases
- Somatic disease that might affect cognitive function adversely
- Usage of anticoagulants
- Prior radiation- or chemo-therapy possibly affecting CNS
- Relevant cancer or other serious disease with expected survival < 5 years
- Fish meal intake more than 2 times a week
- Regularly intake of Omega-3 supplements over the last 3 months
Sites / Locations
- Akershus university hospital, Sykehusveien 25Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Arm 1a; Placebo
Arm 2a; Omega-3 capsules
Arm Description
Valid for the first 24 weeks of the study. Arm 1a: placebo, soft gelatine capsule containing 1000 mg olive oil, refined.
Valid for the first 24 weeks of the study. Arm 2a; Omega-3, (1000 mg fill weight per capsule) containing omega-3 ethyl ester concentrate with a high proportion of DHA.
Outcomes
Primary Outcome Measures
Cognitive function
CERAD 10 word memory test relative to placebo
Secondary Outcome Measures
Cognitive function
Cantab RT test relative to placebo
Cognitive function
Cantab PAL test relative to placebo
Cognitive function
Cantab SWT test relative to placebo
Blood PBMC betaAmyloid mid-domain assay
IVD assay
CSF betaAmyloid 1-42
IVD assay
CSF TAU
IVD assay
CSF Phospho-TAU
IVD assay
MRI ASL
MRI procedure
MRI WML
MRI procedure
MRI DTI
MRI procedure
Full Information
NCT ID
NCT03926351
First Posted
March 11, 2019
Last Updated
April 23, 2019
Sponsor
University Hospital, Akershus
Collaborators
BASF AS, Pre Diagnostics AS
1. Study Identification
Unique Protocol Identification Number
NCT03926351
Brief Title
High Dose Omega 3 in People at Risk for Dementia
Official Title
A Randomized, 24 Week Parallel-group Placebo-controlled (Phase 2) Pilot-study of High Dose Omega 3 (DHA) in People at Risk for Dementia
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
October 2019 (Anticipated)
Study Completion Date
October 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Akershus
Collaborators
BASF AS, Pre Diagnostics AS
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is the efficacy of a docosahexaenoic acid (DHA)-rich dietary supplement in improving key dementia-related mechanisms and cognitive function in older people at risk for dementia. This is a randomized placebo-controlled, 24 weeks, phase 2 study of Omega 3 in people with increased risk of dementia. The aim is to explore the effects of DHA on cognitive performance (CERAD 10 word memory tests, TMT A/B, Stroop Color-Word, FAS, VOSP silhouettes, Cantab-test (RT, PAL, SWT)), biological markers (blood: CRP, NLF, TNF-alpha, MCI-1, PBMC Abeta middomain, Omega-3-index, IL, CSF: NLF, sTREM2, Ab 1-42, total and -phospho-tau) and imaging (MRI: standard structural DDI protocol including Freesurfer and WML measurements, DTI and ASL).
Detailed Description
Earlier trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been moderately promising, but these interventions often suffered from relatively low DHA concentrations. In this trial, the investigators will use a DHA-rich dietary supplement formulated using a self-microemulsifying delivery system to accelerate absorption.
Modification of innate immune activity has already been seen using DHA-rich supplements, and this type of intervention has been shown to ameliorate AD-associated PBMC profiles, and to be associated with improvements in cognition. DHA can cross the BBB, and the resulting CSF concentrations are associated with reduced CSF total tau levels indicating that DHA reduce neurodegeneration, ameliorate Abeta42 induced neuronal damage, and increase microglia Abeta phagocytosis. However, pre-clinical and pre-dementia intervention trials linked to biomarkers for the AD disease process is lacking, and therefore, stratification with respect to stage of disease process has not been performed.
Study cohort: subjects in this pilot study will be recruited from the Norwegian Dementia Disease Initiative (DDI) cohort. The DDI cohort consists of 600 participants with Subjective Cognitive Dedcline (SCD), Mild Cognitive Impairment (MCI) and normal control subjects that have been included at dementia centres across Norway during 2012-2016. Blood samples and cerebrospinal fluid (CSF) have been collected and are stored centrally at Ahus. A comprehensive and highly standarized clinical assessment program has been administered by trained raters (assessors). The investigators are currently performing 2-year follow-up evaluations. Genetic data including APOE-isoforms have been collected as have baseline and follow-up MRIs, PET scans (so far in Oslo and Bergen) and baseline CSF examinations (Ab, total-tau and phosphorus-tau). Cognitive assessments at baseline and follow-up include MMSE and Clinical Dementia Rating (CDR), CERAD 10 word memory test, Clock drawing test, Trail Making Test A and B, Verbal fluency test (FAS), visual recognition test (VOSP silhouettes), Stropp Coloraturas-Word. Data is assembled in a customised database (UiO secure server (TSD)), developed based on XNAT (http://www.xnat.org) and also connected to pipelines for image analysis. A selection from CANTAB MCI test battery including RTI (reaction time), PAL (paired associates learning test), and SWM (spatial working memory).
Study design: All subjects included in the intervention study will have completed 2-year follow-up in the DDI study prior to inclusion and will be on stable medication at least 3 months prior to baseline examinations. Based on the existing electronic CRF for DDI, social e-RCT-CRFs will be developed and programmed into the proprietary XNAT database. Patients fulfilling the inclusion criteria will be identified by a nurse at the memory outpatient clinics and will be given a short information letter regarding the study. Written consent will be asked for. Thereafter, a medical and neurological examination of the patient will be performed, including a medical history and medication use.
This initial pilot study is a minor feasibility study with 40 subjects randomised equally to either of 2 treatment groups for 24 weeks,
Omega-3 3 capsules/day Placebo 3 capsules/day
Each study participant will take 3 capsules in the morning for the 24-week study period. The study may be followed by a larger and statistical valid study. Patients will be randomized (by means of a computerized program) to identically appearing set of capsules with Omega-3 or placebo, 1:1 (produced by BASF AS).
Optional extension study: Participants will be offered another 24-week Omega-3 capsule supply after study end, and a follow-up assessment after 1 year will be conducted, comparing those with and without continuous Omega-3 treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dementia, Inflammation, Mild Cognitive Impairment, Cognitive Decline, SCD, Cognitive Dysfunction, Pathologic Processes, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurocognitive Disorders, Mental Disorder, Cognition Disorders
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A randomized, 24-week parallel-group placebo-controlled (Phase 2) pilot-study of high dose Omega 3 (DHA) in people at risk for dementia
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double blinded
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1a; Placebo
Arm Type
Placebo Comparator
Arm Description
Valid for the first 24 weeks of the study. Arm 1a: placebo, soft gelatine capsule containing 1000 mg olive oil, refined.
Arm Title
Arm 2a; Omega-3 capsules
Arm Type
Experimental
Arm Description
Valid for the first 24 weeks of the study. Arm 2a; Omega-3, (1000 mg fill weight per capsule) containing omega-3 ethyl ester concentrate with a high proportion of DHA.
Intervention Type
Dietary Supplement
Intervention Name(s)
Omega-3 capsules
Intervention Description
BASF AS is the developer of the gelatine capsules containing Omega-3 ethyl ester from fish oil concentrate, as the dietary (nutritional) ingredient. The additional capsule fill ingredients are food additives permitted in food supplements according to Regulation (EC) No 1333/2008 on Food additives.
Intervention Type
Dietary Supplement
Intervention Name(s)
Olive oil
Intervention Description
Soft gelatine capsule containing 1000 mg olive oil, refined.
Primary Outcome Measure Information:
Title
Cognitive function
Description
CERAD 10 word memory test relative to placebo
Time Frame
Baseline to 24 weeks
Secondary Outcome Measure Information:
Title
Cognitive function
Description
Cantab RT test relative to placebo
Time Frame
Baseline to 24 weeks
Title
Cognitive function
Description
Cantab PAL test relative to placebo
Time Frame
Baseline to 24 weeks
Title
Cognitive function
Description
Cantab SWT test relative to placebo
Time Frame
Baseline to 24 weeks
Title
Blood PBMC betaAmyloid mid-domain assay
Description
IVD assay
Time Frame
Baseline to 24 weeks
Title
CSF betaAmyloid 1-42
Description
IVD assay
Time Frame
Baseline to 24 weeks
Title
CSF TAU
Description
IVD assay
Time Frame
Baseline to 24 weeks
Title
CSF Phospho-TAU
Description
IVD assay
Time Frame
Baseline to 24 weeks
Title
MRI ASL
Description
MRI procedure
Time Frame
Baseline to 24 weeks
Title
MRI WML
Description
MRI procedure
Time Frame
Baseline to 24 weeks
Title
MRI DTI
Description
MRI procedure
Time Frame
Baseline to 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 50 years
SCD or MCI
No evidence of neurodegeneration (i.e. CSF phospho and total tau-levels below cut-off)
Scandinavian mother tongue
Completed 2-year follow-up in the DDI-study
Stable medication for at least 3 months prior to baseline exam
Exclusion Criteria:
Dementia (defined as MMSE < 26 and/or CDR >/= 1))
Other dementia giving disease than AD
Other brain disease
Significant depression
Unstable coronary heart disease or heart failure in need of treatment
Systemic inflammatory diseases
Somatic disease that might affect cognitive function adversely
Usage of anticoagulants
Prior radiation- or chemo-therapy possibly affecting CNS
Relevant cancer or other serious disease with expected survival < 5 years
Fish meal intake more than 2 times a week
Regularly intake of Omega-3 supplements over the last 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tormod Fladby, MD PhD
Phone
+4792817764
Email
tormod.fladby@medisin.uio.no
First Name & Middle Initial & Last Name or Official Title & Degree
Erik Christensen, MD PhD
Phone
+4795939918
Email
erik@pre-diagnostics.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tormod Fladby, MD PhD
Organizational Affiliation
University Hospital, Akershus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Akershus university hospital, Sykehusveien 25
City
Lørenskog
ZIP/Postal Code
1478
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tormod Fladby
Phone
+4767960000
Email
tormod.fladby@medisin.uio.no
12. IPD Sharing Statement
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High Dose Omega 3 in People at Risk for Dementia
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